Molecular mechanisms for the evolution of multicellular complexity in social amoebas

生物学家想要了解像我们这样复杂的多细胞生物是如何从简单的单细胞祖先进化而来的。从理论上讲，我们知道这是如何发生的：早期生物体基因的自发突变导致其后代的发育程序发生微小变化。这有时会导致一个更成功地繁殖的改进的成年体，从而逐渐取代早期的形式。然而，要真正理解这个过程并证明它确实发生了，我们必须追溯哪些基因发生了突变，以及这种突变如何改变基因功能。我们还需要知道哪些发育机制是由突变基因调控的，以及改变的发育机制最终是如何产生改进的成年形态的。因为不可能从像我们这样高度进化的动物身上获得如此详细的信息，所以我们在社会性阿米巴虫身上研究了这个问题。这些生物在进食时以单细胞的形式生活。然而，当饥饿时，它们聚集在一起形成多细胞子实体，其中一部分细胞被保存为孢子。其他细胞形成茎和其他结构来支撑孢子团。这种生活方式依赖于细胞的相互协作和专业化。在进化过程中，社会性变形虫从形成结构的基础物种（10-100个细胞，只有两种细胞类型）发展到形成大型复杂结构的物种（超过100万个细胞，多达五种细胞类型）。其中一种，盘状棘球蚴，被许多实验室用作模型系统，以了解细胞如何移动、进食、繁殖和相互交流。在世界范围内已分离出100多种已知的社会性变形虫。为了了解这些物种如何逐渐变得更加复杂和彼此不同，我们首先使用DNA数据构建了社会变形虫的家谱。这棵树表明，社会阿米巴虫有四个主要群体，而盘状阿米巴虫是最近形成的群体中的一员。接下来，我们测量了大量的特征，这些特征决定了所有75个物种的典型大小和形态。通过在家谱上绘制这些字符，我们可以追溯到哪个字符是先出现的，以及它是如何逐渐变得更复杂的。最近，我们参与了代表这四个群体的物种的基因组测序。这些项目几乎已经完成，为我们研究基因在进化过程中是如何变化的提供了巨大的机会。在这项研究中，我们将把对基因变化的详细分析与我们之前对进化过程中发生的形式变化的分析结合起来。这应该给我们一些指示，哪些基因的变化可能导致了新形式的出现。通过操纵有问题的基因并观察其对物种形态的影响，我们将能够证明某种特定的基因变化是某种特定形态变化的实际原因。通过这种方式，我们将能够解开进化所使用的遗传机制，这些机制产生了我们在现代多细胞生物中看到的各种各样的形式。

Biologists want to understand how complex multicellular organisms like ourselves have evolved from their simple single-celled ancestors. We know in theory how this happened: Spontaneous mutations in the genes of earlier organisms caused small changes in the developmental program of their offspring. This sometimes resulted in an improved adult that more successfully reproduced, and therefore gradually replaced the earlier form. However, to really understand this process and prove that it actually occurred, we have to trace back which genes were mutated and how this mutation changed gene function. We also need to know which developmental mechanisms were regulated by the mutated genes and how the altered developmental mechanism eventually produced the improved adult form. Because it is not possible to obtain such detailed information for highly evolved animals like ourselves, we investigate this problem in the social amoebas. These organisms live as single cells when they are feeding. However, when starved, they come together and form a multicellular fruiting body, in which a proportion of cells is preserved as spores. The other cells form a stalk and other structures to support the spore mass. This life style depends on mutual collaboration and specialization of cells. In the course of evolution the social amoebae have progressed from basal species that formed structures with 10-100 cells and only two cell-types, to species that form large complex structures with over 1 million cells and up to five cell types. One species, D.discoideum, is used by many laboratories as a model system to understand how cells move, eat, propagate and communicate with each other. Over a 100 known social amoeba species have been isolated worldwide. To understand how these species gradually became more complex and different from each other, we first used DNA data to construct a family tree of the social amoebas. This tree showed that there are four major groups of social amoebas and that D.discoideum is a member of the group that was formed most recently. We next measured a large number of characters that determine the typical size and form of all 75 species. By plotting these characters on the family tree we can trace back which character came first and how it gradually changed into greater complexity. Most recently we were involved in sequencing the genomes of species that represent each of the four groups. These project are almost completed and offer us enormous opportunities to study how genes have changed during evolution. In this study we will combine a detailed analysis of changes in genes with our earlier analysis of the changes in form that occurred during evolution. This should give us indications which changes in the genes might have been responsible for the appearance of novel forms. By manipulating the gene in question and observing its effect on the form of the species, we will be able to prove that a particular genetic change was the actual cause for a specific change in form. In this manner we will be able to unravel the genetic mechanisms that have been used by evolution to generate the enormous variety of forms that we see in modern multicellular organisms.